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Selection of resistance by piperacillin during Pseudomonas aeruginosa endocarditis
E D Letendre1, R Mantha, P L Turgeon
1Division of Microbiology and Infectious Diseases, Hôpital Saint-Luc, Montreal, Québec, Canada.
Abstract:
The mechanisms responsible for emergence of resistance during antimicrobial therapy were investigated in isolates obtained from a patient suffering from Pseudomonas aeruginosa endocarditis. The strain was first isolated from blood cultures obtained upon admission of the patient. It was sensitive to piperacillin, ticarcillin and tobramycin. Piperacillin-tobramycin therapy was therefore instituted and led to a rapid improvement of the patient's condition. Unfortunately, the patient subsequently became febrile again and blood cultures continued to yield P. aeruginosa. However, the organism isolated was now resistant to piperacillin and other penicillins tested. Cell-free extracts of the pre- and post-therapy isolates were analyzed for their beta-lactamase activity. The susceptible pre-therapy strain did not produce significant levels of beta-lactamase. In contrast, the post-therapy strain produced high levels of the enzyme. Induction experiments indicated that the production of beta-lactamase was constitutive in the post-therapy isolate. Thus, piperacillin therapy has led to the selection of resistant mutants which produced high levels of beta-lactamase constitutively. This was associated with relapse of the infection and therapeutic failure.
Insights
Antimicrobial resistance emerged in Pseudomonas aeruginosa during therapy due to high-level, constitutive beta-lactamase production. This resistance led to treatment failure and infection relapse.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa endocarditis is a serious infection requiring effective antimicrobial therapy.
- Emergence of antimicrobial resistance during treatment can lead to therapeutic failure.
Purpose of the Study:
- To investigate the mechanisms of resistance development in Pseudomonas aeruginosa during antimicrobial therapy.
- To analyze beta-lactamase activity in pre- and post-therapy isolates.
Main Methods:
- Isolates of Pseudomonas aeruginosa were obtained from a patient with endocarditis before and after piperacillin-tobramycin therapy.
- Beta-lactamase activity was measured in cell-free extracts of both susceptible and resistant isolates.
- Induction experiments were performed to assess the nature of beta-lactamase production.
Main Results:
- The pre-therapy isolate was susceptible to piperacillin and produced low levels of beta-lactamase.
- The post-therapy isolate exhibited resistance to piperacillin and produced high levels of beta-lactamase.
- Beta-lactamase production in the resistant isolate was found to be constitutive.
Conclusions:
- Piperacillin therapy selected for Pseudomonas aeruginosa mutants with constitutive high-level beta-lactamase production.
- This resistance mechanism was associated with the relapse of endocarditis and treatment failure.
- Understanding resistance mechanisms is crucial for optimizing antimicrobial therapy strategies.